CLEARANCE OF POSTPRANDIAL AND LIPOLYTICALLY MODIFIED HUMAN HDL IN RABBITS AND RATS

Triglyceride (TG) enrichment of high density lipoproteins (HDL) in hyp ertriglyceridemic states renders the particles vulnerable to lipolysis , which reduces their size. In the present study we modified the size and composition of HDL in vivo in hypertriglyceridemic humans by admin istering a bolus of intravenous heparin, and tested the subsequent cle arance of the isolated HDL particles in rabbits and rats. HDL was isol ated by ultracentrifugation from 21 moderately hypertriglyceridemic hu mans, 5 h after ingestion of a high fat meal and then 15 min after an intravenous heparin bolus (60 U/kg). Postprandial large TG-rich prehep arin HDL and small, TG-poor postheparin HDL were labeled with either I -125 or I-131. The clearance of apoA-I associated with each HDL tracer was determined by injecting the tracers 1) simultaneously (n = 13) an d 2) sequentially (n = 8) into male New Zealand White rabbits, an hepa tic lipase-deficient animal, and 3) by injecting the tracers simultane ously into male Sprague-Dawley rats (n = 8), an animal that has hepati c lipase. Dieaway curves of each radiolabeled tracer were analyzed usi ng a two-pool model that assumes the existence of an intravascular poo l in dynamic equilibrium with an extravascular pool. In the rabbit stu dies, the fractional catabolic rate (FCR) of small, postheparin TG-poo r HDL was greater than the FCR of the larger TG-rich HDL (11% greater in the simultaneous study, P < 0.001, and 45% greater in the sequentia l study, P < 0.001). Opposite results were observed in rats as large T G-rich preheparin particles showed a greater FCR (1.8-fold) than small er TG-poor postheparin HDL (P < 0.05). These data suggest that althoug h size and composition of HDL can influence its catabolism, the effect is not always in the same direction and depends on other factors pres ent in vivo.